The long-term objective of this application is to establish the role of human IL-3 in normal and malignant hemopoiesis. Specifically it is proposed to: 1.Establish the critical regions for activity of the IL-3 molecule by carrying out site-directed mutagenesis of the IL-3 gene; chemically synthesizing the IL-3 molecule; developing monoclonal antibodies to IL-3 that inhibit function. A multiple biological and receptor assay system will be used seeking to identify IL-3 mutants with selective function. 2.Study the regulation of production of the IL-3 molecule by examining: the IL-3 mRNA stability and translation; the transcription of the IL-3 gene seeking to identify regulatory sequences and new transcription factors. These studies may lead to new forms of therapies in patients with leukemia by developing specific tools to inhibit the response of leukemic cells to IL-3 or by inhibiting their IL-3 production.